Life Science Encyclopedia

Propylthiouracil (PTU) is a thionamide drug used to treat hyperthyroidism by decreasing the amount of thyroid hormone produced by the thyroid gland. It was approved by the United States Food and Drug Administration in 1947.

Indications

Hyperthyroidism, including Graves disease.

Mode of action

PTU inhibits the enzyme thyroperoxidase, which normally acts in thyroid hormone synthesis to add iodide to the tyrosine residues on the hormone precursor thyroglobulin, thus forming thyroxine. PTU also acts by inhibiting the enzyme 5'-deiodinase (tetraiodothyronine 5' deiodinase), which converts T₄ to the active form T₃. Notably, PTU does not inhibit the action of the sodium-dependent iodide transporter located on follicular cells' basolateral membranes. Inhibition of this step requires competitive inhibitors such as perchlorate and thiocyanate.

Pharmacokinetics

Administration is oral with peak serum concentrations occurring in one hour, and actively concentrated to the thyroid gland. Depending on several patient variables, however, euthyroid status may not be achieved until 2–4 months after treatment initiation. Of note, the drug is approximately 70% protein-bound and significantly ionized at normal physiologic pH. As a result, there is little placental transfer or distribution to breast milk. In contrast, the antithyroid agent methimazole has higher levels of both placental transfer and breast milk distribution and is therefore contraindicated in pregnant/lactating females.

The plasma half-life is one hour and is not altered appreciably by the thyroid status of the patient. Due to the concentration in the thyroid, however, dosing intervals may last 8 hours or longer. Less than 10% of the drug is excreted unchanged, the remaining fraction undergoing extensive hepatic metabolism via glucuronidation.

Side effects

Agranulocytosis- a decrease of white blood cells in the blood. Symptoms and signs of agranulocytosis include infectious lesions of the throat, the gastrointestinal tract and skin with an overall feeling of illness and fever. A decrease in blood platelets (thrombocytopenia) also may occur. Since platelets are important for the clotting of blood, thrombocytopenia may lead to problems with excessive bleeding.

Propylthiouracil (PTU) is generally well-tolerated with side effects occurring in 1 of every 100 patients. The most common side effects are related to the skin and include rash, itching, hives, abnormal hair loss, and skin pigmentation.Other common side effects are swelling, nausea, vomiting, heartburn, loss of taste, joint or muscle aches, numbness and headache,allergic reactions, and hair whitening.

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